| Project/Area Number |
10214204
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | National Institute for Physiological Sciences |
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Principal Investigator |
IKENAKA Kazuhiro Okazaki National Institutes, National Institute for Physiological Sciences, Professor, 生理学研究所, 教授 (00144527)
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| Co-Investigator(Kenkyū-buntansha) |
BABA Hiroko Tokyo University of Pharmacology and Life Science, Professor, 薬学部, 教授 (40271499)
FUJIMOTO Ichiro Center for Integrative Biochemistry, Research Associate, 統合バイオサイエンスセンター, 助手 (70264710)
KAGAWA Tetsushi National Institute for Physiological Sciences, Research Associate, 生理学研究所, 助手 (50270484)
中平 健祐 埼玉医科大学, 第三生理学教室, 講師 (10260043)
岩崎 靖乃 岡崎国立共同研究機構, 生理学研究所, 助手 (40311196)
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| Project Period (FY) |
1998 – 2001
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥87,000,000 (Direct Cost: ¥87,000,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 2000: ¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 1999: ¥27,000,000 (Direct Cost: ¥27,000,000)
Fiscal Year 1998: ¥27,500,000 (Direct Cost: ¥27,500,000)
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| Keywords | myelinated fiber / ion channel clustering / Node of Ranvier / paranode / 有髄神経軸索 / ミエリン / 電位依存性カリウムチャネル / 脱髄性疾患 / オリゴデンドロサイト / 神経伝導 / ランビエの紋輪 |
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| Research Abstract |
Recently it has been shown that the function of oligodendrocyte (OL) is not only to insulate the axons but also to direct ion channel clustering on the axonal surface. In this study we identified the molecules involved in the interaction between OL and axon, and investigated the mechanisms underlying the induction of ion channel clustering.
1) Differentiation and maturation of OLs are regulated by signals derived from the axons. One of the signals known is Jagged-Notch signaling. We identified that expression of Mash1, a transcriptional factor, is suppressed by the activation of this signaling. We also found that development of OL is abnormal in the Mash1 knock-out mouse indicating that Mash1 is playing an important role in OL development in vivo.
2) We found that the presence of myelin membrane is not required in the initial clustering of the voltage gated sodium channels, but is required for the maturation of the nodes. On the other hand the myelin membrane and paranodal junctions are essential for the potassium channels to cluster at proper sites. Moreover, they are also necessary for the maintenance of the clusters. We also found that sulfatide and CD9 play important roles in transporting molecules, such as NF155, that are essential for the paranodal junction formation to the paranodes.
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